Prefrontal-midline thalamic circuitry in rodents at the intersection of cognition, emotion and motivation

The prefrontal cortex (PFC) exerts top-down control over distributed neural systems to coordinate cognition, emotion, and motivated behavior, with the midline thalamus (MTh) seated as an anatomical interface through which these signals are routed to cortical and limbic networks. Among midline nuclei, the nucleus reuniens (RE) of the ventral MTh and paraventricular nucleus (PV) of the dorsal MTh share extensive connectivity with the medial PFC (mPFC), establishing parallel but anatomically distinct PFC-thalamic circuits. PFC projections to RE provide a route through which the mPFC can influence the hippocampal formation (HF), while reciprocal RE projections to the PFC provide a pathway for integrating mnemonic, affective, and contextual information into PFC processing. In contrast, PFC interactions with PV engage the amygdala, nucleus accumbens, and other regions involved in arousal, stress, motivational, and cognitive states. Importantly, the convergence of PFC projections onto both RE and PV, coupled with their divergent downstream connectivity, provides a substrate through which PFC signals can be distributed across distinct functional networks. Consistent with this organization, PFC-RE circuitry contributes prominently to working memory, executive control, and the contextual regulation of behavior, whereas PFC-PV circuitry participates in the regulation of arousal, affective processing, and motivated behavior. Here, we review the anatomical and functional organization of PFC interactions with RE and PV in rodents, emphasizing the midline thalamus as a key conduit through which the PFC recruits distributed limbic networks to guide behavior.